Ovarian cancer remains one of the most aggressive and fatal gynecologic malignancies, characterized by high rates of recurrence and poor long-term survival, largely attributable to the emergence of multidrug resistance. Although significant progress has been made in cytoreductive surgical techniques and platinum- and taxane-based chemotherapy, as well as the incorporation of targeted therapies and immunotherapies, therapeutic resistance remains a formidable obstacle in clinical management. The multifactorial nature of drug resistance encompassing genetic alterations, epigenetic reprogramming, metabolic adaptations, and the influence of the tumor microenvironment demands a deeper mechanistic understanding to inform the development of next-generation therapeutic strategies.

This special issue seeks to present a comprehensive and cutting-edge synthesis of recent advances in elucidating the molecular and cellular determinants of drug resistance in ovarian cancer. We welcome original research articles, authoritative reviews, and expert perspectives focusing on the identification and validation of predictive biomarkers, elucidation of chemoresistance and targeted therapy resistance pathways, design of novel nanotechnology-enabled drug delivery systems, and rational combinatorial treatment approaches aimed at circumventing resistance and improving clinical outcomes.

Relevant topics related to this special issue:

1. Mechanisms of Drug Resistance

• Molecular mechanisms underlying platinum and taxane resistance

• Role of epithelial-mesenchymal transition (EMT) and cancer stem cells in drug resistance

• DNA damage repair pathways (BRCA mutations, homologous recombination deficiency) and therapy resistance

• Epigenetic regulation contributing to chemoresistance

• Metabolic reprogramming and its role in drug resistance

• Exosomal communication in transferring drug-resistant phenotypes

2. Tumor Microenvironment and Drug Resistance

• Impact of hypoxia, immune evasion, and stromal interactions

• Role of cancer-associated fibroblasts and extracellular matrix

• Tumor immune microenvironment and immune checkpoint resistance

3. Novel Biomarkers for Predicting Drug Response

• Genomic, transcriptomic, proteomic, and metabolomic signatures

• Liquid biopsy-based biomarkers (ctDNA, circulating exosomes)

• Role of non-coding RNAs (miRNAs, lncRNAs, circRNAs) in drug resistance

4. Overcoming Drug Resistance: Therapeutic Innovations

• Novel small molecules targeting resistant pathways

• Repurposing old drugs to overcome chemoresistance

• Combination therapies with PARP inhibitors, PI3K inhibitors, and immune checkpoint inhibitors

• Nanotechnology-based drug delivery systems targeting drug-resistant ovarian cancer cells

5. Immunotherapy and Resistance

• Mechanisms of resistance to immune checkpoint inhibitors

• CAR-T and NK cell therapies for drug-resistant ovarian cancer

• Tumor immune escape mechanisms

6. Clinical Advances and Challenges

• Current clinical trials targeting drug-resistant ovarian cancer

• Translating bench side discoveries into bedside therapies

• Real-world challenges in managing drug-resistant ovarian cancer patients

7. Future Perspectives

• Personalized and precision medicine approaches

• Artificial intelligence and machine learning in predicting drug resistance

• Multi-omics integration for developing predictive models

This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.

We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or contact the Editor-in-Chief.

The potential contributions of “stem cells” to ovarian and tubal biology are becoming more apparent with time. Whether they be embryonic or adult stem cells, be of a “normal” cell lineage or cells that have acquired stem-like properties (i.e., cancer stem cells), these unique cells can positively or negatively impact ovarian and tubal homeostasis. Stem cells of the ovary and tube include germ cells, cells that evolve to become thecal or granulosa of the follicle, stromal or epithelial cells of the ovary, and the oviduct.

The dynamic nature of these individual reproductive structures and their collective cellular subtypes suggests that the functional contributions of their unique stem cells will be equally diverse and complex. Their contributions in maintaining the cyclic changes associated with the development/maturation of the oocyte or follicle, response to injury (i.e., wound healing of the ovarian surface epithelium in response to ovulation or luteal development in response to an LH surge, etc.), or seeding the microenvironment of the oviduct allowing for the bidirectional activity of germ cells have yet to be fully explored. Additionally, stem cells or cells that take on stem-like properties likely play a role in the pathology of the ovary or tube, giving rise to benign and or malignant tumors.

A better understanding of the contributions of these specialized cells may prove helpful in maintaining fertility as well as the prevention and or treatment of aberrant/malignant conditions. The proposed focused issue seeks to compile reviews, original scientific reports, and commentaries, centralizing the most recent knowledge of ovarian and tubal stem cells for our audience.

We are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or contact the Editor-in-Chief.